Schizophrenia and bipolar disorder are a set of complex, polygenic illnesses that cause enormous human suffering. Little is known about their molecular etiology, although their high heritability suggests that genome sequence variation must contain important clues. Early strategies to identify the genetic contributions to complex diseases included linkage analysis and candidate gene association studies, but were limited by sample size and (in retrospect) an insufficient appreciation of the complexity of these disorders. We now understand that these disorders are influenced by many genetic and environmental factors, few if any of which are deterministic, and almost all of which have required large, well-powered studies to discover and replicate.
